Although the concept of chemical messengers regulating gastrointestinal function has been recognized for many years, recent advances in basic research techniques has led to an explosion of information and interest in peptides of the gut. These peptides have been shown not only to exert a myriad of actions on the gastrointestinal tract, but also to have profound influences on the function of most of the body's organ systems. The wide- spread distribution and actions of gut peptides has led to a broadened base of investigative interest that crosses traditional clinical disciplines and scientific boundaries. Advances in cell biology, biochemistry, and molecular biology have provided tools with which the genetic or molecular links between peptides and clinical digestive disease states may be identified. However, because of the disparate nature of the demands of clinical and basic science, relatively little progress has been made in approaching some of these questions in a unified and broad-based manner. Thus, it is the purpose of this Center to promote interaction between clinical and basic scientists of many disciples with the aim of disseminating new information and catalyzing collaborative research efforts directed at elucidating the role of gut peptides in molecular pathophysiology of digestive diseases. The Center, through its Core laboratories, provides a collective expertise which has enabled investigators to widen the scope of their research. In the previous funding period the 5 existing Cores (Radioimmunoassay/Radioligand, Tissue Culture, Molecular Biology, Histochemistry, and Biochemistry) focused their activities on the primary goals to serve as an intellectual resource, to house specialized equipment and innovative technology, and to perform numerous services for Center investigators. Extensive use of these resources has greatly expanded and enriched the base of investigators that are involved in gastrointestinal research at the University of Michigan. In the current application we propose 2 additional Cores (Cell Biology and In Vitro Studies) to extend the capabilities of the Center even further. Through the mechanism of pilot/feasibility project funding, investigators have pursued new areas of research as well as developed talented young associates in their laboratories. Indeed, during the previous funding period, 25 of the 26 completed projects have resulted in ongoing research initiatives. In summary, the Center has become the fulcrum of activity that galvanizes the research activities of the large and established group of investigators in gut peptides that exists at the University of Michigan. Through the current application, we are seeking to continue and expand the Center with the hope that together the group will approach questions of fundamental importance in the pathophysiology, diagnosis, and treatment of digestive diseases in man.